These studies examine the possibility that alterations in the expression of G protein α subunits occur during desensitization of adrenergic responses in the cardiovascular system. To desensitize adrenergic receptors, rats were infused with norepinephrine (NE) subcutaneously (0.1 mg/kg/h) for 3 or 6 days using osmotic minipumps. G protein α subunits and their mRNAs were then measured in the aorta and heart using selective antibodies and cDNA probes. Infusion of NE for 6 days significantly decreases the levels of G<sub>sα</sub>, G<sub>iα</sub> and G<sub>oα</sub> in the aorta. The mRNAs for the α subunits are not altered in the aorta after NE infusion for 3 or 6 days indicating that reduced mRNA expression does not account for the decreased proteins. In the atrium and ventricle the levels of G<sub>sα </sub>decrease after NE infusion for 3 days but then return to control levels by day 6. The levels of atrial and ventricular G<sub>iα</sub> are unaltered after NE infusion for 3 days but increase significantly by day 6. G<sub>oα</sub> levels do not change in the atrium or ventricle on either day. The level of G<sub>i2α</sub> mRNA increases after NE infusion for 6 days and may account for the increased αi protein. The levels of the other G<sub>α</sub> mRNAs do not change in the atrium or ventricle. These results demonstrate that expression of G protein α subunits is altered during cardiovascular desensitization, raising the possibility that modulation of the α subunits may contribute to reduced adrenergic responsiveness.